Program Overview

TEM8: A Biomarker Across Multiple Solid Tumors

Tumor endothelial marker 8, or TEM8, is a surface protein that is highly expressed on endothelial cells and cancer-associated fibroblasts, which are both central players in the tumor microenvironment across multiple solid tumor cancers, including breast, colon, lung, and pancreatic cancers. TEM8 shows limited expression on cells outside of the tumor microenvironment, making it a clear and precise beacon to enable anti-cancer payloads to be delivered to these key cells while minimizing the opportunity for off-target toxicity.


Importance of Targeting Endothelial Cells and Cancer-Associated Fibroblasts

Endothelial cells and cancer-associated fibroblasts are believed to be important targets for tumor-fighting therapies because they facilitate cancer progression in a number of ways. Research indicates that they support tumor cell growth, promote angiogenesis (or the creation of tumor-nourishing vasculature), and mediate tumor-promoting inflammation and immunosuppression. Because of the activity of cancer-associated fibroblasts and endothelial cells in the tumor microenvironment, tumors are able to survive and thrive through evading current therapeutic approaches and/or developing resistance mechanisms, resulting in cancer progression and metastases. TEM8 has the potential to directly target the cancer-associated fibroblasts and endothelial cells as well as indirectly target the primary cancer cells via a bystander effect.


Potential Utility in Multiple Modalities

We believe our TEM8-directed therapeutic antibodies could serve as a cornerstone across multiple therapeutic modalities, including antibody drug conjugates (ADCs), NK cell engagers and CAR-T cell therapies, among others. We are currently focused on examining TEM8-directed ADCs to more fully understand this protein’s potential in the fight against cancer.

Pre-clinical Activity

Program History & Preclinical Activity

There have been approximately 160 publications on TEM8 over the past 20 years, including research showcasing promising findings for TEM8 as a relevant cancer biomarker. Nevertheless, to date, TEM8 has largely remained unexplored therapeutically.

BVD’s TEM8 discovery research was conducted under a cooperative research and development agreement (CRADA) with the National Cancer Institute. We are currently generating preclinical data on TEM8-directed ADCs and have advanced them to the pre-investigational new drug (IND) stage.

We have generated promising preclinical data in TEM8-directed ADC constructs in multiple cancers, including ovarian, breast, lung and pancreatic cancer models. In these studies, our TEM8-directed ADC constructs prolonged survival, blocked metastasis, and augmented the efficacy of conventional chemotherapy agents without evidence of toxicity. Building on this preclinical evidence, as we advance toward first-in-human clinical studies, we are investigating the optimal initial cancer indications and patient populations and a variety of ADC linker/payload combinations.

ADC Opportunity

TEM8’s Opportunity in ADCs

We believe TEM8-directed therapeutic antibodies have the potential to be used beneficially across multiple modalities. We have initially prioritized TEM8-directed antibody drug conjugates (ADCs) to leverage the lower risk profile of the well-established ADC modality against the novelty of TEM8 as a target.

TEM8 has key characteristics that make it an optimal ADC-directed target:

Predominantly expressed on cells in the tumor microenvironment, with low expression on normal, healthy cells

Demonstrates broad tumor expression, enabling the flexibility to advance ADCs that can address multiple solid tumor indications

Unique biology may allow for different ADCs to be effective via different mechanisms

As we continue to advance TEM8 biology in the translational setting, including an understanding of optimal cancer indications, and de-risk our TEM8 therapeutic antibodies in the clinic via TEM8-directed ADCs, we plan to build on this knowledge to pursue modalities that represent increasingly higher technology hurdles, including NK cell engagers and CAR-T therapies.